| 佟常青,李梦佳,孙文奇,陈佳易,刘 燕,陈子杰,宋月晗.温胆汤影响粪菌移植诱导的广泛性焦虑障碍小鼠海马组织miRNA的表达[J].,2023,(9):1601-1607 |
| 温胆汤影响粪菌移植诱导的广泛性焦虑障碍小鼠海马组织miRNA的表达 |
| WenDan Decoction Affects miRNA Expression in Hippocampus of Mice with Generalized Anxiety Disorder Induced by Fecal Microbiota Transplantation |
| 投稿时间：2022-10-25 修订日期：2022-11-21 |
| DOI：10.13241/j.cnki.pmb.2023.09.001 |
| 中文关键词: 广泛性焦虑障碍 海马 miRNA 粪菌移植 |
| 英文关键词: Generalized anxiety disorder Hippocampus miRNA Fecal microbiota transplantation |
| 基金项目:国家自然科学基金面上项目（81874427）；北京中医药大学校级科研横向发展基金项目（2021-HXFZJJ-016） |
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| 中文摘要: |
| 摘要 目的：探究人源粪菌移植诱导的广泛性焦虑障碍模型小鼠海马组织miRNAs的表达变化及温胆汤对miRNAs的调控作用。方法：实验组经过14天的抗生素洗脱及14天5次的粪菌移植，最后7天给药治疗。实验结束后，通过旷场实验与高架实验检测是否发生焦虑样改变。采用高通量测序方法，分析实验组小鼠海马miRNAs的表达水平，结合网络分析及富集分析方法得到关键miRNAs，并通过RT-PCR实验进行验证。结果：旷场实验中，焦虑模型组较正常模型组移动总距离（P<0.05）、中央格停留时间（P<0.01）及穿格次数（P<0.05）显著降低，经温胆汤治疗后，除总距离外均显著升高（P<0.05）；高架实验中，焦虑模型组较正常模型组开放臂进入次数百分比（P<0.05）和开放臂停留时间百分比（P<0.01）显著降低，经温胆汤治疗后均显著升高（P<0.01）；高通量测序结果显示，实验组重叠且方向一致的miRNAs有12个，其中显著差异的关键miRNAs共9个，注释得到353个靶基因。KEGG结果显示，miRNA可能通过MAPK信号通路、谷氨酸能神经通路、钙信号通路、mTOR信号通路参与调控过程。GO结果显示，miRNA可能通过DNA转录的正调控、突触囊泡胞外分泌的调节、突触前组装调节、神经元动作电位的传播、谷氨酸能突触参与调控过程。RT-PCR结果显示，温胆汤可能通过调控miR-26a-1-3p等miRNAs达到治疗作用。结论：焦虑患者肠道菌群失常导致miR-7a-5p、miR-3077-3p、miR-26a-1-3p等miRNAs异常表达，温胆汤通过调节miR-26a-1-3p等miRNAs达到治疗作用。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the changes of miRNAs expression in hippocampus of mice with human-derived fecal microbiota transplantation induced generalized anxiety disorder model and the regulatory effect of WenDan Decoction on miRNAs. Methods: The experimental groups underwent 14 days of antibiotic elution and 5 fecal microbiota transplants over 14 days, followed by WenDan Decoction for the last 7 days. At the end of the experiment, anxiety-like changes were detected by open field test and elevated plus maze test. The expression levels of miRNAs in the hippocampus of the experimental mice were analyzed by high-throughput sequencing. The key miRNAs were obtained by a combination of enrichment and network analysis methods and validated by RT-PCR. Results: In the open field test, the total distance (P<0.05), time of central zone (P<0.01), and number of zone (P<0.05) were significantly lower in the anxiety model group compared to the control model group. Except for the total distance, the rest were significantly higher after treatment with WenDan Decoction (P<0.05). In the elevated plus maze test, the percentage of entries to the open arms (P<0.05) and the percentage of time spent in the open arms (P<0.01) were significantly lower in the anxiety model compared to the control model group, and both were significantly higher after treatment with WenDan Decoction (P<0.01). High-throughput sequencing results showed that there were 12 overlapping and directionally consistent miRNAs in the experimental group, with 9 significantly different key miRNAs, and 353 target genes were obtained from the annotation. KEGG analysis showed that miRNAs may be involved in the regulation of MAPK signaling pathway, glutamatergic pathway, calcium signaling pathway, and mTOR signaling pathway. The results of GO analysis showed that miRNAs may be involved in the regulation of the positive regulation of DNA transcription, the regulation of presynaptic assembly, the propagation of neuronal action potentials and glutamatergic synapses. RT-PCR results showed that the therapeutic effect of WenDan Decoction may be achieved through the regulation of miRNAs such as miR-26a-1-3p. Conclusion: Dysbiosis of intestinal flora in anxious patients leads to abnormal expression of miRNAs such as miR-7a-5p, miR-3077-3p, miR-26a-1-3p and so on. The therapeutic effect of WenDan Decoction is achieved by regulating miRNAs such as miR-26a-1-3p. |
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